We present an accurate and reliable method for the detection of wall perforation during the excimer-laser micro-drilling of glass ampoules and vials. The method is based on the detection of shock waves generated in the air during the drilling process using a laser-beam deflection probe. An analysis of the detected optodynamic signals gives important information about the progress of the drilling process, and we take this as the basis for the presented online process-monitoring method. We show that a significant change in the signal's amplitude is observed when the wall of a liquid-filled ampoule is perforated and the exit process point is in contact with the liquid, and that this signal change can serve as an indicator of wall perforation. We have verified this optodynamic method by examining the processed holes using optical and electron microscopy as well as with a non-destructive gas-leakage test method. The described method was employed for the production of test ampoules used for the adjustment of a high-voltage leak-detection device in a pharmaceutical production line. Holes with a diameter of less than 10 µm were produced in the walls of 0.5 mm thick glass ampoules using a XeCl excimer laser.